T cell mimicry in inflammatory heart disease

Inflammatory heart diseases such as myocarditis and rheumatic heart disease result from the infiltration of the myocardium or valve with T cells and macrophages that result in scarring of the myocardium or valve and alteration in cardiac function. Our studies of T cells from these diseases have identified cardiac myosin in both rheumatic carditis and myocarditis as an important autoantigen. In rheumatic heart disease, streptococcal M protein specific T cells migrate to valves. By investigating streptococcal M protein and cardiac myosin in the Lewis rat model of myocarditis and valvulitis, T cell mimicry is supported as a potential mechanism in disease. Structural and immunological mimicry between the streptococcal M protein and cardiac myosin is shown directly in the Lewis rat model. Rat T cell lines demonstrate mimicry between cardiac myosin and M protein, and T cells isolated directly from inflammatory lesions in myocarditis respond to streptococcal M protein peptides. Studies in BALB/c mice also support the immunological crossreactivity of T cells primed against cardiac myosin with streptococcal M protein peptides containing cardiac myosin homologies. T cell lines produced from the Lewis rat specific to the cardiac myosin like sequences of streptococcal M protein migrated to the valves after passive transfer of the M protein specific T cell lines. In coxsackieviral myocarditis in the MRL mouse strain, cardiac myosin mimicking M protein peptide NT4 was found to induce tolerance and prevent coxsackieviral induced myocarditis, suggesting T cell mimicry between coxsackievirus and streptococcal M protein, both of which are associated with inflammatory heart disease. T cell mimicry between cardiac myosin and microbial antigens such as the streptococcal M protein may prime the immune system for inflammatory heart disease.     

Vaccination with FimA from Streptococcus parasanguis Protects Rats from Endocarditis Caused by Other Viridans Streptococci

The FimA protein of Streptococcus parasanguis is a virulence factor in the rat model of endocarditis, and immunization with FimA protects rats against homologous bacterial challenge. Because FimA-like proteins are widespread among the oral streptococci, the leading cause of native valve endocarditis, we evaluated the ability of this vaccinogen to protect rats when challenged by other streptococcal species. Here we report that FimA vaccination produced antibodies that cross-reacted with and protected against challenge by the oral streptococci S. mitis, S. mutans, and S. salivarius. FimA thus has promise as a vaccinogen to control infective endocarditis caused by oral streptococci.     

Paecilomyces javanicus endocarditis of native and prosthetic aortic valve

A 41-year-old diabetic woman developed endocarditis of the aortic valve caused by Paecilomyces javanicus six years after insertion of a porcine mitral valve heterograft. The patient died shortly after aortic valve replacement. Autopsy revealed vegetations of the aortic heterograft, valve ring abscess and ascending aortitis due to Paecilomyces. There was no involvement of the mitral valve heterograft. Lesions due to mycotic emboli were found in the kidneys, spleen, and brain. Cultures of the surgically removed aortic valve and of the kidney at autopsy produced rapid growth of P. javanicus. The gross and microscopic pathologic and cultural characteristics of this organism are described with a review of the literature. Previously reported cases of Paecilomyces endocarditis occurred only in prosthetic heart valves. This is the first known report of P. javanicus endocarditis of a native valve and its prosthetic heart valve heterograft.     

Corynebacterium jeikeium endocarditis: a systematic overview spanning four decades

Skin flora is an important source of microorganisms that cause infective endocarditis. While staphylococcal and beta-hemolytic streptococcal species are well-recognized components of skin flora that can cause infective endocarditis, other skin flora rarely produce endocardial infection. One species of Corynebacterium has received the most attention, Corynebacterium jeikeium. This bacterium, a gram-positive rod that is a strict aerobe, is known to cause mechanical prosthetic valve infection and vancomycin is generally required for treatment of this multidrug-resistant organism. Following treatment of an unusual case of bioprosthetic valve endocarditis due to C. jeikeium, a Medline search for English-language articles published from January 1966 to October 2004 was performed. Reports of C. jeikeium endocarditis cases with culture of either blood or cardiac surgery tissue samples positive for C. jeikeium and with clinical and echocardiographic findings of infective endocarditis were reviewed. Clinical data and results of diagnostic procedures were examined. All 38 patients with C. jeikeium endocarditis reported in the literature had at least one predisposing condition for the development of infective endocarditis. The majority of patients (74%) had involvement of a prosthetic heart valve. The mortality attributed to C. jeikeium endocarditis was 33% and was similar in patients who did and did not undergo valve replacement. This relatively high mortality rate mandates that clinicians be aware of this rare endocardial infection. C. jeikeium is a rare cause of endocarditis and it more commonly infects prosthetic valves. Careful scrutiny is required when C. jeikeium is isolated from a blood culture, particularly in patients with underlying prosthetic cardiac valves.     

Antibodies to capsular polysaccharides are not protective against experimental Staphylococcus aureus endocarditis.

The protective efficacy of antibodies to the Staphylococcus aureus capsular polysaccharide was examined in a rat model of catheter-induced endocarditis. Capsular antibodies were induced either by active immunization with killed S. aureus or by passive immunization with hyperimmune rabbit antiserum to S. aureus. Control rats were injected with phosphate-buffered saline or passively immunized with normal rabbit serum or rabbit antiserum to a nonencapsulated strain. Animals with indwelling catheters were challenged intravenously with 5 x 10(4) to 4 x 10(6) CFU of the homologous S. aureus strain (capsular serotype 5 strain Reynolds or serotype 1 strain SA1 mucoid). Both immunized and control rats developed S. aureus endocarditis. The numbers of S. aureus cells recovered from the blood and aortic valve vegetations of immunized rats were similar to those of control rats, indicating that capsule-specific antibodies were not protective. To determine whether the presence of an indwelling catheter interfered with antibody-mediated protection against S. aureus endocarditis, catheters were removed 2 h after insertion in additional groups of rats. An inoculum of 10(8) CFU of strain Reynolds was needed to provoke endocarditis in rats catheterized for 2 h, compared with 5 x 10(4) CFU for rats with indwelling catheters. Passively transferred capsular antibodies were not protective since both immunized and nonimmunized animals developed endocarditis, and quantitative cultures of blood and valvular vegetations revealed no differences between immunized and control animals. The findings of this study indicate that antibodies to the capsular polysaccharide are not protective in the rat model of experimental S. aureus endocarditis.     

Pathologic findings in native infective endocarditis

BackgroundThere are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis.MethodsWe prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention.ResultsThere were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11 (10%) multiple valve replacements. Underlying valve disease was present in 26 (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases; calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease, 1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with streptococcal infection (p = .001). Absence of underlying valve disease was associated with intravenous drug abuse (p = .01) and dialysis dependent renal disease (p = .006). Intravenous drug abuse was associated with staphylococcal infection (p = .03). Vegetations were present in 80 (75%) of cases, and on the nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and neutrophilic microabscesses were associated with staphylococcal infection (p = .03). Epithelioid macrophages with palisading features mimicking necrobiotic granulomas were seen in 42 (40%) valves and more frequently associated with streptococcal infection (p = .03). As expected, the presence of valve necrosis and acute inflammation decreased with an increase in time with respect to symptomatic onset.ConclusionHistologic findings that mimic autoimmune inflammation are frequent in infective endocarditis and associated with streptococcal infection. Risk factors for infective endocarditis include calcific valve disease.     

Inflammation and infection in nine surgically explanted Medtronic Freestyle stentless aortic valves.

BACKGROUND: The Medtronic Freestyle valve is fixed in glutaraldehyde at zero pressure on the cusps and treated with alpha-amino oleic acid. This valve reportedly has excellent clinical and hemodynamic results, but little has been reported about its long-term pathology. METHODS AND RESULTS: Nine Freestyle valves explanted between 2003 and 2005 were reviewed to assess the reasons for bioprosthesis failure (six implanted at our institution). All valves were examined in detail, using histochemistry and immunohistochemistry to identify the cellular response. One Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. Average implant duration was 52.8+/-35.5 months. Four valves were explanted for infective endocarditis, three for aortic insufficiency, two for aortic stenosis with cusp calcification seen in five valves, pannus and thrombus in all valves and a chronic inflammatory reaction involving the xenograft arterial wall seen in eight of nine valves. This was associated with significant damage to the porcine aortic wall in seven cases, and cusp myocardial shelf damage in six cases. CONCLUSIONS: In this series of valves, we found (1) infective endocarditis; (2) pannus, thrombus, and calcification; and (3) unusual and significant inflammatory reaction and aortic tissue damage, which could by itself lead to aortic incompetence.     

Fatal Vibrio fetus endocarditis: Report of one case and review of the literature

Summary Clinical, bacteriologic, and autopsy findings in a case of a 67-year-old man confirmed the diagnosis of Vibrio fetus endocarditis of the aortic, mitral, and tricuspid valve. To our knowledge, this is the first case to involve three valves. The bacterial endocarditis was superimposed on an old, probably rheumatic, endocarditis of the aortic valve, with minimal involvement of the mitral and tricuspid valves. A review of the literature indicates that the aortic valve is the most frequent site of V. fetus endocarditis.     

Endocarditis in a dog due to infection with a novel Bartonella subspecies.

Vegetative valvular endocarditis involving the aortic and, to a lesser extent, mitral valves was diagnosed echocardiographically in a 3-year-old spayed female Labrador retriever. Historically, the dog had been treated with tetracycline hydrochloride and prednisolone for positive seroreactivity to Ehrlichia canis and antinuclear antigens. Although three aerobic and anaerobic blood cultures failed to grow bacteria, blood cultured simultaneously by the lysis centrifugation technique grew a fastidious, gram-negative organism. Despite an initial therapeutic response, the owner elected euthanasia 17 days later. Necropsy confirmed aortic and mitral valvular endocarditis. Bacteria phenotypically similar to Bartonella species were visualized in the heart valve by light and electron microscopy, and Bartonella DNA from a frozen heart valve was amplified by PCR. Subsequent phenotypic and genotypic characterization of the isolate, including biochemical testing, cellular fatty acid analysis, DNA hybridization, and sequencing of the 16S rRNA gene indicated that this organism, which can induce endocarditis in dogs, is a novel Bartonella subspecies containing an insertion sequence unique among currently recognized Bartonella species. The name Bartonella vinsonii subsp. berkoffii subsp. nov. will be proposed for this organism.     

Evaluation of antibiotic therapy following valve replacement for native valve endocarditis

We retrospectively evaluated 105 patients at the Mayo Clinic between 1970 and 2006 with native valve endocarditis who underwent acute valve surgery. The objective was to determine if outcomes differed based on whether they had received an antibiotic regimen recommended for native valve endocarditis or one for prosthetic valve endocarditis. Fifty-two patients had streptococcal and 53 had staphylococcal infections. Patients with each type of infection were divided into two groups: the first received postoperative monotherapy (with a beta-lactam or vancomycin), and the second received combination therapy (with an aminoglycoside for streptococcal infection, and gentamicin and/or rifampin for staphylococcal infection). The duration and types of antibiotics given pre- and postoperatively, valve cultures results, antibiotic-related adverse events, relapses, and mortality rates within 6 months of surgery were analyzed. Cure rates were similar regardless of the regimen administered. With the small number of patients in each group, a multicenter study with a larger cohort of patients is needed to better define optimal postoperative treatment regimens in this population.     

Analysis of adherence of Streptococcus defectivus and endocarditis-associated streptococci to extracellular matrix.

Pathogenesis of nutritionally variant streptococcal (NVS) endocarditis initiates with bacterial attachment to and colonization of the damaged heart valve surface. Underlying extracellular matrix (ECM) exposed to the environment during damage to cardiac endothelium provides additional receptors that could be involved in bacterial adherence. The ability of NVS and endocarditis-associated streptococci to bind ECM was investigated by using an enzyme-linked immunosorbent assay system that incorporated ECM secreted by baby hamster kidney and human umbilical vein endothelial cells in culture. Streptococcus defectivus, the major species isolated from NVS endocarditis cases, bound ECM of fibroblasts and endothelial cells, indicating that the ECM molecule involved in the binding was a common constituent of diverse matrices. The specific binding of S. defectivus to ECM was demonstrated by saturation binding and specific antibody inhibition studies. Of the 15 S. defectivus strains analyzed, 13 bound ECM, whereas Streptococcus adjacens and NVS serotype III strains were unable to bind the matrix. This selective binding suggested that S. defectivus binds to heart valves through a mechanism different from those of other NVS in subacute bacterial endocarditis. A survey of non-NVS streptococcal endocarditis isolates demonstrated that S. mutans, S. mitis, S. sanguis, and S. faecalis also bound ECM, whereas other viridans species were unable to bind the matrix.     

Infective endocarditis of bicuspid pulmonary valve

Infective endocarditis of the cardiac valves mainly involves the aortic mitral valves and less frequently the tricuspid valve. Isolated pulmonary valve involvement is extremely rare with few cases reported in literature. We present a case of a 34-year-old female who presented with sudden onset breathlessness and cardiac failure. A complete autopsy showed an uncommon congenital bicuspid pulmonary valve, which was also affected by infective endocarditis.     

Chemotherapy of experimental streptococcal endocarditis: Part III Failure of a bacteriostatic agent (tetracycline) in prophylaxis 1

Bacteriostatic agents are frequently recommended as alternatives to penicillin for prophylaxis of bacterial endocarditis. To test the efficacy of this group of antimicrobials, prophylaxis of experimental streptococcal endocarditis was attempted with tetracycline. The number of streptococci colonizing the aortic valves of rabbits was not affected by inhibitory levels of tetracycline, but multiplication was checked. Streptococcis urvived in vegetations for seven days despite the continuous presence of tetracycline, and multiplied when the drug was withdrawn. It is therefore suggested that bacteriostatic agents may be valueless for prophylaxis of bacterial endocarditis.     

Contribution of sialic acid-binding adhesin to pathogenesis of experimental endocarditis caused by Streptococcus gordonii DL1

An insertional mutation in hsa, the gene encoding the sialic acid-binding adhesin of Streptococcus gordonii DL1, resulted in a significant reduction of the infection rate of the organism and an inflammatory reaction in the rat aortic valve with experimental endocarditis, suggesting that the adhesin contributes to the infectivity of the organism for heart valves.     

Fluorescence in situ hybridization to improve the diagnosis of endocarditis: a pilot study

Infective endocarditis is a rare but life-threatening disease associated with high mortality. Early diagnosis of the causative microorganism is critical to patient outcome. However, conventional diagnostic methods are often unsatisfactory in achieving this goal. As a proof of concept, we applied fluorescence in situ hybridization (FISH) for detection and identification of bacteria in histological sections of heart valves. Biopsy specimens from 54 suspected endocarditis patients were obtained during valve surgery and analysed via FISH. Specimens were screened with a probe panel that identifies the most common bacteria implicated in endocarditis. Results were compared with those of culture-based diagnostics and clinical data. Discrepant results were subjected to comparative sequence analysis of PCR-amplified 16S rRNA genes. FISH detected bacteria in 26 of the 54 heart valves. FISH allowed successful diagnosis of infective endocarditis in five of 13 blood culture-negative cases and in 11 of 37 valve culture-negative cases, showing the bacteria within their histological context. This technique allows the simultaneous detection and identification of microorganisms at the species or genus level directly from heart valves and might be a valuable tool for diagnosis of endocarditis.     

Electron microscopy and serological features of a patient with Q fever prosthetic valve endocarditis.

The clinical, serological and electron microscopic findings in a 47 year old woman with bioprosthetic valve coxiella endocarditis occurring 15 years after streptococcal endocarditis are described. The patient underwent valvular surgery a total of four times to control symptoms and remains well on medical therapy more than two years after her last operation.     

Vegetative endocarditis in a Waldrapp ibis

A case of bacterial vegetative endocarditis in a Waldrapp ibis is described. Lesions were present on both atrio-ventricular valves and there were thromboembolic lesions in brain, lung and myocardium. A streptococcal origin is suspected.     

Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats.

FimA, a surface-associated protein of Streptococcus parasanguis, is associated with initial colonization of damaged heart tissue in an endocarditis model (D. Burnette-Curley, V. Wells, H. Viscount, C. Munro, J. Fenno, P. Fives-Taylor, and F. Macrina, Infect. Immun. 63:4669-4674, 1995). We have evaluated the efficacy of recombinant FimA as a vaccine in the rat model of endocarditis and investigated in vitro the mechanism for the protective role of immunization. FimA-immunized and nonimmunized control animals were catheterized to induce heart valve damage and infected intravenously with 10(7) CFU of wild-type S. parasanguis FW213 bacteria. The presence of bacteria associated with platelet-fibrin vegetations 24 h postchallenge was evaluated. Immunized rats were significantly less susceptible to endocarditis (2 cases among 34 animals) than the control group (21 cases among 33 animals) (P < 0.001). Incubation of S. parasanguis FW213 with rabbit anti-FimA immune serum decreased the mean percent adherence (0.34% of added cells) to platelet-fibrin matrix in vitro compared with that of preimmune normal serum (5.04% of added cells; P < 0.001). Adsorption of immune serum with FimA-positive S. parasanguis FW213 yielded antiserum that failed to block adherence to the platelet-fibrin matrix. We assessed the vaccine potential of FimA as a common immunogen able to provide cross-protection in streptococcal endocarditis by determining the occurrence and expression of fimA in the viridans group streptococci and enterococci. We detected the presence of fimA homologs by Southern hybridization and PCR amplification analyses and determined by immunoblotting the expression of FimA-like proteins among a variety of streptococci and enterococci that frequently cause endocarditis. Eighty-one percent (26 of 32) of streptococcal and enterococcal strains isolated from bacteremic patients expressed proteins that comigrated with FimA and were reactive with polyclonal anti-FimA serum. Streptococcal DNA from strains that were positive by Western blot (immunoblot) analysis hybridized to the full-length fimA probe. Our studies suggest that FimA immunization results in antibody-mediated inhibition of bacterial adherence, a critical early event in the pathogenesis of endocarditis. Our data demonstrate that a majority of streptococcal strains associated with endocarditis have genes that encode FimA-like proteins. Taken together, these results suggest that FimA is a promising candidate for an endocarditis vaccine.     

Mycobacterium fortuitum prosthetic valve endocarditis: a case for the pathogenetic role of biofilms

BackgroundProsthetic valve endocarditis presents unique challenges for both diagnosis and treatment. A potential role of biofilm has been hypothesized in the pathogenesis of these infections.MethodsA patient with infective endocarditis involving a stentless (Freestyle) porcine prosthetic aortic valve with annular abscess and paravalvular leak 8 months after implantation is reported.ResultsThe infected valve did not show vegetations or perforations, but histiocytic inflammation was seen along the endocardial surfaces of the valve. Auramine–rhodamine staining revealed many acid-fast organisms associated with the inflammation. There was also an acellular matrix material with ultrastructural features of biofilm. Blood cultures grew Mycobacterium fortuitum, a biofilm-associated microbe.ConclusionsThe role of biofilm in prosthetic valve endocarditis is discussed. The importance of microscopy for prosthetic valves, even when no vegetations are present, is highlighted along with correlation of pathologic findings with culture results.     

Q fever endocarditis; not always expected

Q fever endocarditis is a chronic disease with protean manifestations. The clinical and serological manifestations of nine patients diagnosed as having Q fever endocarditis during a 19-year period are reviewed. Four patients (44%) required valve replacement due to congestive heart failure. Three of these four patients were diagnosed as having Q fever endocarditis only after elective valve surgery, by histopathological examination of the valve and subsequent serological tests. Prior to surgery they were afebrile and had no other symptom or sign indicative of endocarditis. The antibiotic treatment and the decreasing titres of Q fever antibodies of all nine patients during several years of follow-up are summarized. Careful assessment of heart valves for histopathological evidence of inflammation is suggested, even after elective replacement. If found, clinical and laboratory evaluation should include determination of anti-Coxiella burnetti antibodies.